Propofol Attenuates Early Brain Injury After Subarachnoid Hemorrhage In Rats

【background and Objective】Subarachnoid hemorrhage(subarachnoid hemorrhage,SAH) is a disease with high disability and mortality rate, the most common cause of SAH is ruptured cerebral aneurysm. a SAH may induce early brain injury(EBI) and delayed brain injury, which was manifested as cerebral edema, intracranial hypertension,cerebral infarction, neurological disorders, disturbance of consciousness, which may relevant to the inflammation, cerebral vasospasm, apoptosis, etc. The specific pathogenesis and treatment strategy is still poorly understood in current, which remains to be further studied. Propofol as a new kind of intravenous anesthetic, with rapid onset and no accumulation after infusion, wake up quickly and completely, fewer adverse reactions, etc. has been widely used in clinical. Researchs had found that propofol has a protective effect on the brain, but there does not have reaearch applied the propofol in the subarachnoid hemorrhage. Therefore, this study will establish a rat model of subarachnoid hemorrhage then received treatment with propofol. To investigate the potential molecular mechanisms of EBI after SAH and the neuroprotection of propofol.【 Method 】 80 SD rats were randomly divided into sham operation group(sham-operated + vehicle), SAH group(SAH + vehicle), SAH + P10(SAH + propofol10 mg / kg), SAH + P50(SAH + propofol 50 mg / kg). Sprague Dawley rats underwent subarachnoid hemorrhage(SAH) by endovascular perforation then received treatment with propofol(10 or 50 mg/kg) or vehicle after 2 and 12 h of SAH. Rats were treated with normalsaline as the vehicle control at the same volume as propofol. SAH grading,neurological scores, brain water content, Evans blue extravasation, the myeloperoxidase activity, and malondialdehyde(MDA) content were measured 24 h after SAH.Expression of nuclear factor erythroid-related factor 2(Nrf2), nuclear factor-kappa B(NF-κB) p65, and aquaporin 4(AQP4) expression in rat brain were detected by Western blot. Expression of cyclooxygenase-2(COX-2) and matrix metalloproteinase-9(MMP-9)were determined by reverse transcription-polymerase chain reaction(RT-PCR).Expressions of tumor necrosis factor-α(TNF-α) and interleukin-1β(IL-1β) were assessed by ELISA.【Result】SAH grade between the control group and the experimental group is not statistically significant(P>0.05). Compare to the sham group the neurological scores of SAH group significantly decreased(P<0.01), brain water content significantly increased(P<0.01), Evans blue extravasation(P<0.01), the myeloperoxidase activity(P<0.01), and MDA content(P<0.01) were significantly increased in SAH group compare to Sham group. Furthermore, expression of Nrf2 in rat brain was upregulated by propofol, and expression of NF-κB p65, AQP4, COX-2, MMP-9, TNF-α and IL-1βin rat brain were attenuated by propofol.【Conclusion】Neurological scores, brain water content, Evans blue extravasation,the myeloperoxidase activity, and MDA content were significantly reduced by propofol.Furthermore, expression of Nrf2 in rat brain was upregulated by propofol, and expression of NF-κB p65, AQP4, COX-2, MMP-9, TNF-α and IL-1β in rat brain were attenuated by propofol..